Fig. 3

Receptor signalling pathway for all-trans retinoic acid (at-RA). Cellular retinoic acid binding proteins (CRABP) protect at-RA from non-specific degradation and transport it to the nucleus. Retinoid receptors recognise and bind to a DNA sequence motif termed a retinoic acid response element (RARE). This motif is composed of two repeats of a hexameric motif, separated by a variable number of nucleotides (N)—in this schematic we show a five-nucleotide separator sequence (DR5-RARE) as highlighted in red. Once at-RA is liganded to a receptor, this initiates a signalling cascade in the canonical mechanism whereby nuclear co-activators are recruited. Expression of proximal genes to the RARE sequence is upregulated via the action of the co-activators which alter chromatin availability, for example, histone acetylation